a) Field of the Invention
The process of solid phase extraction (SPE) makes it possible to separate complex mixtures of substances such as mixtures of microorganisms, vegetable and animal samples and synthetic mixtures containing combinatorial and parallelized syntheses for subsequent analysis. The separating process consists in that the complex substance mixture is initially adsorbed in suitable extraction phases, then separated by elution in one or more separation steps, each with one or more separation stages, and the obtained fractions are concentrated, if necessary, by another SPE step or are adjusted on a desired solvent.
b) Description of the Related Art
The complex work sequences for carrying out the process of solid phase extraction always comprise the same process steps, such as the conditioning of the extraction phases (sorbents, resins or separating phases), the supplying of specimens, washing, and elution. Identical process steps which sometimes run repeatedly in different sequences are excellent candidates for automation.
Since the supplied substances (specimens or solvents) do not flow through the extraction phase exclusively due to gravitational force in many applications, the substance is forced through the extraction phase by generating a vacuum below the extraction phase or an overpressure above the extraction phase. Technical apparatus has been developed for both principles. In this connection, systems making use of a vacuum suction technique have proven disadvantageous. The vacuum that can be generated remains limited to one bar and with a plurality of cartridges per vacuum channel the pressure compensation takes place through the best “running” cartridges (vessel containing an extraction phase), so that a complete elution often does not take place in poorly “running” cartridges. In particular With biological specimens, the viscosity and the particle proportion is often so unfavorable that some cartridges elute incompletely when the process is carried out simultaneously in a plurality of cartridges with the vacuum suction technique (e.g., Nachr. Cheni. Tech. Lab. 44; 1969; No. 4; page M18).
In known devices which press the specimen through the extraction phase with overpressure, each cartridge is individually sealed independently from one another. For example, the STRATEC Elektronik GmbH company offers an automatic pipettor, known as VIVACE, with an expansion module FEX which is suitable for carrying out the SPE process. In order to generate a positive pressure on the extraction phase, an appropriate tool of one of the two pipetting arms of the VIVACE is placed on the upper end of the column (cartridge end) in a gastight manner and the necessary pressure is built up with a suitable inert gas. Each of the two pipetting arms is outfitted with a pipetting needle. The pipetting needle can be freely positioned within a plane by means of the linear adjustment of the pipetting needle at the pipetting arm in one coordinate direction and the movement of the pipetting arm in a coordinate direction vertical to the latter. In this way, pipetting can be carried out from virtually any commonly used vessel. Regardless of the circumference of the vessels or the distances at which they are positioned from one another below the pipetting arm, the pipetting tip can be moved to the vessels in such a way that it stands above the vessels exactly in the center.
The demand for the use of vessels with different circumferences results from the different volumes which depend, for example, on their concentration to be taken up and dispensed by means of the pipetting needles. For an economical use of substances and a reproducible volume take-up, the entire volume to be taken up must be taken up by completely emptying a vessel. Since the relative lift required for this purpose between the pipetting needle and vessel bottom should be as small and as constant as possible regardless of the capacity of the vessel, there is a demand for the use of vessels of the same height with different circumferences having correspondingly different capacities. However, vessels for dispensing the substance—even if they have different capacities—could also, in principle, have the same circumference but a different height because immersion is not required for dispensing in the vessel. However, for automation, a constant lift is also advantageous in this case, so that there is also a demand in this case for the possibility of using vessels with different circumferences.
Vessels for receiving (specimen vessels) and dispensing (cartridges) are available as individual vessels, also already arranged in a rack in a two-dimensional arrangement with modular sizes or grid dimensions (center distances) of a×b (a represents the grid dimension of vessels arranged in a row and b represents the grid dimension of the vessels arranged in a column).
As an alternative to the two-dimensional arrangement of individual vessels, there are monolithic blocks of specimen vessels and cartridges in which the actual vessels are formed by chambers with grid dimensions a×b.
The cross section of the individual vessels and chambers is usually round or rectangular. Polygonal shapes are also known. In arrangements with round and square cross sections: a=b.
The grid dimensions are adapted to those of commercially available microtiter plates or other multi-vessel systems.
With regard to the automation of simultaneous receiving and dispensing of specimens from and into vessel arrangements of different grid dimensions, there is the particular problem of providing a needle arrangement which is suitable for emptying and filling these vessels and which can also be sealed relative to these vessels.
The prior art does not disclose any apparatus for carrying out the SPE method that is suitable for receiving the substances from two-dimensional arrangements of specimen vessels of different grid dimensions with a two-dimensional needle arrangement and dispensing the substances in a two-dimensional cartridge arrangement under pressure.